INTERACTIONS OF CRF AND NE IN NUCLEUS ACCUMBENS SHELL

描述（申请人摘要）：该系统失调与精神疾病如抑郁症有关。CRF被认为是对压力的综合自主神经、神经内分泌和行为反应的中枢介质。CRF的行为效应通常类似于轻度压力或兴奋的情况；已提出去甲肾上腺素（NE）通过增强神经元感觉输入的显著性来调节觉醒和警觉性。因此，CRF和NE可以相互作用，调节生物体对不断变化的环境条件所表现出的基本行为特征。伏隔核（AcbSh）的壳亚区含有高浓度的CRF和NE，并被认为整合皮层、边缘、自主神经和运动区域加工的信息；因此，AcbSh可以很好地调节生物体的基本行为特征，以响应其动态的外部环境。因此，AcbSh可能是CRF和NE系统发挥作用的重要位点，并可能在调节生物体的基本行为曲目中相互作用。本研究旨在研究CRF和NE在AcbSh中的行为作用，以及该区域内这些系统之间可能相互作用的神经化学和解剖学基础。这项工作可能为描述生物体维持行为稳态的基本机制提供了重要的第一步；对这些基础的理解可能最终有助于我们深入了解抑郁症和焦虑症等疾病中失调的一些过程，这些疾病的特征是对环境突发事件的不适当行为反应的表达。

DESCRIPTION (applicant's abstract): Dysregulation of the system has been associated with psychiatric disorders such as depression. CRF is thought to function as a central mediator of integrated autonomic, neuroendocrine, and behavioral responses to stress. The behavioral effects of CRF often resemble conditions of mild stress or arousal; norepinephrine (NE) has been proposed to regulate arousal and vigilance by enhancing the salience of sensory inputs to neurons. Thus, CRF and NE could interact to modulate the fundamental behavioral profile that an organism exhibits in response to its changing environmental conditions. The shell subregion of the nucleus accumbens (AcbSh) contains dense concentrations of CRF and NE, and is thought to integrate information processed in cortical, limbic, autonomic, and motor areas; AcbSh is thereby very well positioned to regulate the basic behavioral profile of an organism in response to its dynamic external milieu. AcbSh could thus be an important site in which CRF and NE systems act and possibly interact in the regulation of an organism's fundamental behavioral repertoire. The present proposal seeks to examine the behavioral roles of CRF and NE in the AcbSh, and the neurochemical and anatomical substrates of possible interactions between these systems within this region. This work may provide an important first step in characterizing the basic mechanisms through which an organism maintains behavioral homeostasis; understanding of these substrates might ultimately shed insight into some of the processes that become dysregulated in illnesses such as depression and anxiety disorders that are characterized by the expression of inappropriate behavioral responses to environmental contingencies.